Differential activation of N-methyl-d-aspartic acid and kainic acid receptors in the pedunculopontine nucleus of the rat modulates both ascending and descending efferent projections related to preattentional and arousal mechanisms

The reticular activating system (RAS) drives thalamocortical oscillations underlying different states of arousal; i.e. waking, slow wave and rapid eye movement sleep. These studies were aimed at determining how glutamate receptors within the pedunculopontine nucleus (PPN) modulate arousal states by using recordings of the P13 midlatency auditory evoked potential and the postural startle response (SR) in the rat.; Aim I tested that the hypothesis that activation of glutamate (GLU) receptors in the PPN would modulate the P13 potential and SR. Results showed that intracranial microinjection (ICM) of GLU dose-dependently increased the amplitude of the P13 potential, and decreased the amplitude of the SR. Specific GLU antagonists caused a dose-dependent decrease in P13 potential and increase in SR amplitude. Pretreatment with AP5 or GAMS differentially reduced the GLU induced increase in P13 potential and decrease in SR amplitude.; Aim II tested the hypothesis that activation of NMDA receptors in the PPN, known to be involved with the maintenance of waking, would modulate the P13 potential and SR. Results showed that ICM of NMDA dose-dependently increased the amplitude of the P13 potential, and decreased the amplitude of the SR. Pretreatment with AP5 reduced the NMDA induced increase in P13 potential and decrease in SR amplitude.; Aim III tested the hypothesis that activation of kainate (KA) receptors in the PPN, known to be involved with the generation of REM sleep, would modulate the P13 potential and SR. The results showed that ICM of KA dose-dependently increased the amplitude of the P13 potential, and decreased the amplitude of the SR. Pretreatment with GAMS reduced the KA induced increase in P13 potential and decrease in SR amplitude.; Results showed that differential activation and blockade of GLU receptors in the PPN can modulate the P13 potential and SR. Activation of these GLU receptors induced time specific effects. Therefore, KA and NMDA may have different roles in modulating arousal and pre-attentional mechanisms through excitatory ascending projections, and modulate descending inhibitory postural mechanisms.